Article Dans Une Revue Stem Cell Reviews and Reports Année : 2024

Complementary and Inducible creERT2 Mouse Models for Functional Evaluation of Endothelial Cell Subtypes in the Bone Marrow

Michael G Poulos
Pradeep Ramalingam
Agatha Winiarski
  • Fonction : Auteur
Michael C Gutkin
  • Fonction : Auteur
Lizabeth Katsnelson
  • Fonction : Auteur
Cody Carter
  • Fonction : Auteur
Jean-Leon Thomas
  • Fonction : Auteur
Jason M Butler

Résumé

In the adult bone marrow (BM), endothelial cells (ECs) are an integral component of the hematopoietic stem cell (HSC)supportive niche, which modulates HSC activity by producing secreted and membrane-bound paracrine signals. Within the BM, distinct vascular arteriole, transitional, and sinusoidal EC subtypes display unique paracrine expression profiles and create anatomically-discrete microenvironments. However, the relative contributions of vascular endothelial subtypes in supporting hematopoiesis is unclear. Moreover, constitutive expression and off-target activity of currently available endothelialspecific and endothelial-subtype-specific murine cre lines potentially confound data analysis and interpretation. To address this, we describe two tamoxifen-inducible cre-expressing lines, Vegfr3-creER T2 and Cx40-creER T2 , that efficiently label sinusoidal/transitional and arteriole endothelium respectively in adult marrow, without off-target activity in hematopoietic or perivascular cells. Utilizing an established mouse model in which cre-dependent recombination constitutively-activates MAPK signaling within adult endothelium, we identify arteriole ECs as the driver of MAPK-mediated hematopoietic dysfunction. These results define complementary tamoxifen-inducible creER T2 -expressing mouse lines that label functionallydiscrete and non-overlapping sinusoidal/transitional and arteriole EC populations in the adult BM, providing a robust toolset to investigate the differential contributions of vascular subtypes in maintaining hematopoietic homeostasis.

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hal-04886250 , version 1 (14-01-2025)

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Michael G Poulos, Pradeep Ramalingam, Agatha Winiarski, Michael C Gutkin, Lizabeth Katsnelson, et al.. Complementary and Inducible creERT2 Mouse Models for Functional Evaluation of Endothelial Cell Subtypes in the Bone Marrow. Stem Cell Reviews and Reports, 2024, 20, pp.1135 - 1149. ⟨10.1007/s12015-024-10703-9⟩. ⟨hal-04886250⟩
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